Nanolipoprotein-Mediated Her2 Protein Transfection Induces Malignant Transformation in Human Breast Acinar Cultures

ACS Omega ◽  
2021 ◽  
Author(s):  
Wei He ◽  
Angela C. Evans ◽  
William F. Hynes ◽  
Matthew A. Coleman ◽  
Claire Robertson
Keyword(s):  
Malignant Transformation ◽  
Human Breast ◽  
Her2 Protein ◽  
Protein Transfection

scholarly journals Nanolipoprotein mediated Her2 protein transfection induces malignant transformation in human breast acinar cultures

2020 ◽  
Author(s):  
Wei He ◽  
Angela C. Evans ◽  
Matthew Coleman ◽  
Claire Robertson
Keyword(s):  
Breast Cancer ◽  
Malignant Transformation ◽  
Cell Surface Receptor ◽  
Cell Phenotype ◽  
Her2 Overexpression ◽  
Malignant Cells ◽  
Transformation Techniques ◽  
Her2 Protein ◽  
Surface Receptor ◽  
Protein Transfection

AbstractHer2 overexpression is associated with an aggressive form of breast cancer and malignant transformation. We sought to determine if a nano-carrier system could introduce Her2 protein to non-malignant cells and determine the effects on cell phenotype and transcriptome. With stimulation with Her2-NLPs, we observed uptake of Her2 protein and a decreased probability of individual non-malignant cells forming polar growth arrested acinar-like structures. The NLP delivery system alone or Her2-NLPs plus trastuzumab showed no effect on acinar organization rate. Transcriptomics revealed essentially no effect of empty NLPs versus untreated cells whereas Her2-NLPs versus either untreated or empty NLP treated cells revealed upregulation of several factors associated with breast cancer. Pathway analysis also suggested that known nodes downstream of Her2 were activated in response to Her2-NLP treatment. This suggests that Her2-NLPs are sufficient for malignant transformation of non-malignant cells and that this system offers a new model for studying cell surface receptor signaling without genomic modification or transformation techniques.

Discovery of a new phospho-HER2+/FISH- molecular subtype of human breast cancer by functional pathway mapping

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11009-11009
Author(s):  
J. Wulfkuhle ◽  
M. Pierobon ◽  
J. Laird ◽  
V. Espina ◽  
I. L. Liotta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Human Breast Cancer ◽  
Quantitative Methods ◽  
Cancer Tissue ◽  
Fish Analysis ◽  
Major Advance ◽  
Human Breast ◽  
Molecular Phenotype ◽  
Her2 Protein ◽  
Pathway Mapping

11009 Background: Effective treatment of breast cancer through the targeting of the HER2 protein in human breast cancer represents a major advance in oncology, yet the identification of responders has relied on non-quantitative methods (IHC) that measure the erbB2 protein or indirect genomic analysis (FISH) of the erbB2 gene that cannot predict protein pathway activation status. We utilized a new quantitative protein microarray assay to measure total and phosphorylated HER2 in the context of broad-scale EGFR signal pathway mapping in order to generate a new molecular characterization scheme for human breast cancer. Methods: Pure tumor epithelium from 149 frozen pre-treatment human breast cancer tissue specimens (from the I-SPY TRIAL: CALGB 150007/150012, ACRIN 6657) were procured via Laser Capture Microdissection and protein pathway mapping was performed using Reverse Phase Protein Microarrays (RPMA) whereby the activation of 40 key signaling proteins was quantitatively measured at once. Results: While phospho-HER2 and total HER2 as measured by RPMA had excellent concordance with FISH (95%) and IHC (94%), of the 63 cases where both clinical FISH and IHC status of c-erbB2 were known, we discovered that 5/45 (11%) of the FISH-/IHC- cases had phosphorylated HER2 levels as high or higher than the FISH+/IHC positive patients. These results were confirmed and validated by independent analysis with quantitative Western Blot using a separate biopsy specimen from the same patients. Conclusions: A new molecular phenotype of human breast cancer has been identified whereby total levels of HER2 are low yet levels of the phosphorlyated receptor are very high. This molecular phenotype is not detectable by FISH analysis nor by measurement of the total HER2 protein itself. Given the central importance of phosphorylation on effective signal transduction of the EGFR family, we are planning to determine the clinical significance of this finding by retrospective analysis of banked material with outcome, and a prospective clinical trial in I-SPY 2. Support: ACRIN U01 CA079778 ; CALGB CA31964, CA33601; NCI SPORE CA58207. [Table: see text]

Genistein affects HER2 protein concentration, activation, and promoter regulation in BT-474 human breast cancer cells

Endocrine ◽  
2007 ◽  
Vol 32 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Mary S. Sakla ◽  
Nader S. Shenouda ◽  
Pete J. Ansell ◽  
Ruth S. MacDonald ◽  
Dennis B. Lubahn
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Protein Concentration ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Promoter Regulation ◽  
Her2 Protein

scholarly journals Raloxifene and Desmethylarzoxifene Block Estrogen-Induced Malignant Transformation of Human Breast Epithelial Cells

PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27876 ◽  
Author(s):  
Irida Kastrati ◽  
Praneeth D. Edirisinghe ◽  
L-P-Madhubani P. Hemachandra ◽  
Esala R. Chandrasena ◽  
Jaewoo Choi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Malignant Transformation ◽  
Human Breast ◽  
Breast Epithelial Cells ◽  
Breast Epithelial ◽  
Human Breast Epithelial Cells

Virus-Like Particles in a Human Breast Cancer: Structural Similarity to Previously Reported Particles

1973 ◽  
Vol 31 ◽  
pp. 378-379
Author(s):  
G. Kasnic ◽  
S. E. Stewart ◽  
C. Urbanski
Keyword(s):  
Breast Cancer ◽  
Biological Activity ◽  
Human Breast Cancer ◽  
Osteogenic Sarcoma ◽  
Human Tumor ◽  
Structural Similarity ◽  
Cell Tumor ◽  
Human Breast ◽  
Human Tumor Cell ◽  
Type Particle

We have reported the maturation of an intracisternal A-type particle in murine plasma cell tumor cultures and three human tumor cell cultures (rhabdomyosarcoma, lung adenocarcinoma, and osteogenic sarcoma) after IUDR-DMSO activation. In all of these studies the A-type particle seems to develop into a form with an electron dense nucleoid, presumably mature, which is also intracisternal. A similar intracisternal A-type particle has been described in leukemic guinea pigs. Although no biological activity has yet been demonstrated for these particles, on morphologic grounds, and by the manner in which they develop within the cell, they may represent members of the same family of viruses.

Lectin Binding to Human Breast Tumor Cells

1976 ◽  
Vol 34 ◽  
pp. 34-35
Author(s):  
Robert E. Nordquist ◽  
J. Hill Anglin ◽  
Michael P. Lerner
Keyword(s):  
Carcinoma Cell ◽  
Ricinus Communis ◽  
Lectin Binding ◽  
Low Frequency ◽  
Breast Carcinoma Cell Line ◽  
Human Breast ◽  
Human Breast Tumor ◽  
Duct Carcinoma ◽  
Specific Antigens ◽  
Ricin Agglutinin

A human breast carcinoma cell line (BOT-2) was derived from an infiltrating duct carcinoma (1). These cells were shown to have antigens that selectively bound antibodies from breast cancer patient sera (2). Furthermore, these tumor specific antigens could be removed from the living cells by low frequency sonication and have been partially characterized (3). These proteins have been shown to be around 100,000 MW and contain approximately 6% hexose and hexosamines. However, only the hexosamines appear to be available for lectin binding. This study was designed to use Concanavalin A (Con A) and Ricinus Communis (Ricin) agglutinin for the topagraphical localization of D-mannopyranosyl or glucopyranosyl and D-galactopyranosyl or DN- acetyl glactopyranosyl configurations on BOT-2 cell surfaces.

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